Virtuelle (Nano) Welten: PDB Molecule of the Month 34: Dihydrofolate Reductase

Taking Advantage of Differences

Dihydrofolate reductase is used in all organisms, but each organism makes a slightly different version. Over the course of the evolution of life, the plans for dihydrofolate reductase have slowly mutated, making small changes but keeping the essential function the same. As a result, the version from bacteria, shown on the left from PDB entry 3dfr, is smaller and more streamlined than the version in our own cells, shown on the right from PDB entry 1dls. As seen in these structures, both bind similarly to NADPH, shown in green, and to the drug methotrexate, shown in purple. Researchers, however, have developed drugs that take advantage of the differences. For instance, the drug trimethoprim binds about 30,000 times more tightly to the bacterial enzyme. So, it is effective as an antibiotic drug. A low dose of trimethoprim will attack bacteria while leaving the dihydrofolate reductase in our own cells relatively untouched.